乳腺癌组织中STAT3激活的意义

目的:分析STAT3在乳腺癌及癌旁乳腺组织中的激活水平与乳腺癌临床分期的关系,探讨STAT3在乳腺癌发病机制中的作用.方法:乳腺癌手术标本36例,免疫组化SP法检测STAT3蛋白在乳腺癌组织中的表达;凝胶迁移电泳率实验测定STAT3在乳腺癌及癌旁乳腺组织中的激活水平.结果:在临床ⅡA,ⅡB和ⅢA期乳腺癌组织中STAT3激活水平均明显高于同期癌旁乳腺组织(P均＜0.01),ⅡA,ⅡB和ⅢA期乳腺癌组织中STAT3激活水平无显著差异(P＞0.05);STAT3蛋白主要表达于细胞质和细胞核.结论:STAT3可能在乳腺癌的发生发展中有重要的作用;抑制STAT3的激活可能成为治疗乳腺癌的一种新的途径.     

Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group.     

姜黄素对糖尿病大鼠肾组织AP-1的DNA结合活性升高的抑制作用

目的探讨姜黄素对糖尿病大鼠肾组织转录因子活化蛋白-1(activator protein-1,AP-1)的DNA结合活性升高的抑制作用。方法大鼠随机分为正常对照组(A组)、糖尿病组(B组)及姜黄素治疗组(C组),采用腹腔单剂量注射链脲佐菌素(streptozotocin,STZ)65mg/kg建立糖尿病大鼠模型。治疗组给予姜黄素30mg/kg.d腹腔注射。实验第4周各组分别宰杀5只大鼠,取部分右肾皮质,采用电泳迁移率改变分析(elec-trophoresis mobility shift assay,EMSA)检测姜黄素对糖尿病大鼠肾组织AP-1的DNA结合活性的影响,并观察肾组织的病理变化。结果糖尿病大鼠肾组织AP-1的DNA结合活性明显升高,姜黄素对其有显著抑制作用,并减轻糖尿病大鼠肾脏病变。结论姜黄素通过抑制糖尿病大鼠肾组织AP-1的DNA结合活性升高而减轻糖尿病大鼠肾脏病变。     

HIF-1α结合活性及蛋白含量的表达变化在缺氧性肺动脉高压大鼠中的作用和意义

目的 研究HIF-1α结合活性及蛋白含量的表达变化在缺氧性肺动脉高压(HPH)大鼠中的作用和意义.方法 40只成年雄性SD大鼠随机分为对照组(C组)和缺氧3、7、14天和21天组(H3、H7、H14和H21组),每组8只,常压缺氧复制HPH大鼠模型.测各组大鼠平均肺动脉压(mPAP)、右室肥大指数(RVHI)、血管形态学指标;EMSA法检测HIF-1α结合活性的变化,免疫组化、Western blot检测HIF-1α蛋白质表达.结果 (1)缺氧7天后,mPAP开始上升,与对照组比较差异有显著性(P＜0.05).缺氧14天达高水平并维持于此水平.缺氧14天后出现肺血管重塑,RVHI改变.(2)EMSA发现对照组HIF-1α结合活性水平较低,3天组迅速升高,14天组达到高峰.(3)Westem blot发现,HIF-1α蛋白在对照组有一定的表达,缺氧3天组蛋白质明显升高,缺氧7天达高峰,此后保持高水平;免疫组化示HIF-1α蛋白在肺小血管表达不明显,缺氧3天明显升高(0.194±0.017,P＜0.05),7天达到高峰,随后缺氧14天和21天组水平下降.结论 HIF-1a的结合活性及蛋白含量在HPH大鼠均可见明显增高,HIF-1α在大鼠HPH的发病机制中发挥作用.